Chemical exchange saturation transfer (CEST) exploits the chemical exchange of labile protons of an endogenous or exogenous compound with water to image the former indirectly through the water signal. Z-spectra of the brain have traditionally been analyzed for two most common saturation phenomena: downfield amide proton transfer (APT) and upfield nuclear Overhauser enhancement (NOE). However, a great body of brain metabolites, many of interest in neurology and oncology, contributes to the downfield saturation in Z-spectra. The extraction of these “hidden” metabolites from Z-spectra requires careful design of CEST sequences and data processing models, which is only possible by first obtaining CEST signatures of the brain metabolites possessing labile protons. In this work, we measured exchange rates of all major-for-CEST brain metabolites in the physiological pH range at 37 °C. Analysis of their contributions to Z-spectra revealed that regardless of the main magnetic field strength and pH, five main contributors, i.e. myo-inositol, creatine, phosphocreatine, glutamate, and mobile (poly)peptides, account for ca. 90% of downfield CEST effect. The fundamental CEST parameters presented in this study can be exploited in the design of novel CEST sequences and Z-spectra processing models, which will enable simultaneous and quantitative CEST imaging of multiple metabolites: multicolor CEST.

PurposeTo compare two pulsed, volumetric chemical exchange saturation transfer (CEST) acquisition schemes: steady state (SS) and pseudosteady state (PS) for the same brain coverage, spatial/spectral resolution and scan time.MethodsBoth schemes were optimized for maximum sensitivity to amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) effects through Bloch‐McConnell simulations, and compared in terms of sensitivity to APT and NOE effects, and to transmit field inhomogeneity. Five consented healthy volunteers were scanned on a 7 Tesla Philips MR‐system using the optimized protocols at three nominal B1 amplitudes: 1 μT, 2 μT, and 3 μT.ResultsRegion of interest based analysis revealed that PS is more sensitive (P < 0.05) to APT and NOE effects compared with SS at low B1 amplitudes (0.7–1.0 μT). Also, both sequences have similar dependence on the transmit field inhomogeneity. For the optimum CEST presaturation parameters (1 μT and 2 μT for APT and NOE, respectively), NOE is less sensitive to the inhomogeneity effects (15% signal to noise ratio [SNR] change for a B1 dropout of 40%) compared with APT (35% SNR change for a B1 dropout of 40%).ConclusionFor the same brain coverage, spatial/spectral resolution and scan time, at low power levels PS is more sensitive to the slow chemical exchange‐mediated processes compared with SS. Magn Reson Med 77:2280–2287, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

ObjectivesThe purpose was to implement a fast 3D glycosaminoglycan Chemical Exchange Saturation Transfer (gagCEST) sequence at 7 T, test stability and reproducibility in cartilage in the knee in healthy volunteers, and evaluate clinical applicability in cartilage repair patients.MethodsExperiments were carried out on a 7-T scanner using a volume transmit coil and a 32-channel receiver wrap-around knee coil. The 3D gagCEST measurement had an acquisition time of 7 min. Signal stability and reproducibility of the GAG effect were assessed in eight healthy volunteers. Clinical applicability of the method was demonstrated in five patients before cartilage repair surgery.ResultsCoefficient of variation of the gagCEST signal was 1.9%. The reproducibility of the GAG effect measurements was good in the medial condyle (ICC = 0.87) and excellent in the lateral condyle (ICC = 0.97). GAG effect measurements in healthy cartilage ranged from 2.6%-12.4% compared with 1.3%-5.1% in damaged cartilage. Difference in GAG measurement between healthy cartilage and damaged cartilage was significant (p < 0.05).ConclusionsA fast 3D gagCEST sequence was applied at 7 T for use in cartilage in the knee, acquired within a clinically feasible scan time of 7 min. We demonstrated that the method has high stability, reproducibility and clinical applicability.Key Points • gagCEST measurements are stable and reproducible • A non-invasive GAG measurement with gagCEST can be acquired in 7 min • gagCEST is able to discriminate between healthy and damaged cartilage Electronic supplementary materialThe online version of this article (10.1007/s00330-017-5277-y) contains supplementary material, which is available to authorized users.

High field MRI is beneficial for chemical exchange saturation transfer (CEST) in terms of high SNR, CNR, and chemical shift dispersion. These advantages may, however, be counter‐balanced by the increased transmit field inhomogeneity normally associated with high field MRI. The relatively high sensitivity of the CEST contrast to B 1 inhomogeneity necessitates the development of correction methods, which is essential for the clinical translation of CEST. In this work, two B 1 correction algorithms for the most studied CEST effects, amide‐CEST and nuclear Overhauser enhancement (NOE), were analyzed. Both methods rely on fitting the multi‐pool Bloch‐McConnell equations to the densely sampled CEST spectra. In the first method, the correction is achieved by using a linear B 1 correction of the calculated amide and NOE CEST effects. The second method uses the Bloch‐McConnell fit parameters and the desired B 1 amplitude to recalculate the CEST spectra, followed by the calculation of B 1‐corrected amide and NOE CEST effects. Both algorithms were systematically studied in Bloch‐McConnell equations and in human data, and compared with the earlier proposed ideal interpolation‐based B 1 correction method. In the low B 1 regime of 0.15–0.50 μT (average power), a simple linear model was sufficient to mitigate B 1 inhomogeneity effects on a par with the interpolation B 1 correction, as demonstrated by a reduced correlation of the CEST contrast with B 1 in both the simulations and the experiments.